Background and purpose: Systemic lupus erythematosus (SLE) is associated with significant cerebrovascular and neuropsychiatric disease for which multiple pathogeneses have been proposed. Although global cerebral hypoperfusion has been proposed, there are limited data about intracerebral arterial hemodynamics. Transcranial Doppler (TCD) allows portable, high temporal and spatial resolution, noninvasive blood velocity measurements in the middle cerebral arteries, and calculations of standard resistivity (RI) and pulsatility (PI) indices. RI and PI correlate with cerebral hemispheric arteriolar tone, blood flow resistances, and impedances. Accordingly, we hypothesized that there would be significant differences (p < 0.05) in RI and PI between SLE patients and healthy, age and gender matched controls. Methods: TCD was used to measure RI and PI bilaterally on 34 stable SLE patients (35 ± 11 years) and 15 control subjects (34 ± 10 years). Patients and controls had similar, normal blood pressures and were examined in the supine position during normal, resting respiration. RI and PI were determined by a blinded, experienced observer. Results: There were no significant differences in RI and PI bilaterally within each cohort. However, SLE patients had significantly lower average RI and PI values compared with controls: 0.45 ± 0.10 versus 0.52 ± 0.05 (p < 0.05); and 0.65 ± 0.19 versus 0.77 ± 0.12, (p < 0.05); respectively. Conclusions: These preliminary data suggest that RI and PI values in the human middle cerebral artery are significantly lower in SLE compared with controls. These indices indicate that middle cerebral arterial resistances and impedances are decreased in SLE. Under normotensive conditions, the results are consistent with hyperperfusion in SLE with increased arteriolar dilation and increased cerebral blood flow.